The developmental origin of cancers defines basic principles of cisplatin resistance
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The developmental origin of cancers defines basic principles of cisplatin resistance. / Skowron, Margaretha A; Oing, Christoph; Bremmer, Felix; Ströbel, Philipp; Murray, Matthew J; Coleman, Nicholas; Amatruda, James F; Honecker, Friedemann; Bokemeyer, Carsten; Albers, Peter; Nettersheim, Daniel.
In: CANCER LETT, Vol. 519, 28.10.2021, p. 199-210.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - The developmental origin of cancers defines basic principles of cisplatin resistance
AU - Skowron, Margaretha A
AU - Oing, Christoph
AU - Bremmer, Felix
AU - Ströbel, Philipp
AU - Murray, Matthew J
AU - Coleman, Nicholas
AU - Amatruda, James F
AU - Honecker, Friedemann
AU - Bokemeyer, Carsten
AU - Albers, Peter
AU - Nettersheim, Daniel
N1 - Copyright © 2021 Elsevier B.V. All rights reserved.
PY - 2021/10/28
Y1 - 2021/10/28
N2 - Cisplatin-based chemotherapy has been used for more than four decades as a standard therapeutic option in several tumor entities. However, being a multifaceted and heterogeneous phenomenon, inherent or acquired resistance to cisplatin remains a major obstacle during the treatment of several solid malignancies and inevitably results in disease progression. Hence, we felt there was an urgent need to evaluate common mechanisms between multifarious cancer entities to identify patient-specific therapeutic strategies. We found joint molecular and (epi)genetic resistance mechanisms and specific cisplatin-induced mutational signatures that depended on the developmental origin (endo-, meso-, ectoderm) of the tumor tissue. Based on the findings of thirteen tumor entities, we identified three resistance groups, where Group 1 (endodermal origin) prominently indicates NRF2-pathway activation, Group 2 (mesodermal origin, primordial germ cells) shares elevated DNA repair mechanisms and decreased apoptosis induction, and Group 3 (ectodermal and paraxial mesodermal origin) commonly presents deregulated apoptosis induction and alternating pathways as the main cisplatin-induced resistance mechanisms. This review further proposes potential and novel therapeutic strategies to improve the outcome of cisplatin-based chemotherapy.
AB - Cisplatin-based chemotherapy has been used for more than four decades as a standard therapeutic option in several tumor entities. However, being a multifaceted and heterogeneous phenomenon, inherent or acquired resistance to cisplatin remains a major obstacle during the treatment of several solid malignancies and inevitably results in disease progression. Hence, we felt there was an urgent need to evaluate common mechanisms between multifarious cancer entities to identify patient-specific therapeutic strategies. We found joint molecular and (epi)genetic resistance mechanisms and specific cisplatin-induced mutational signatures that depended on the developmental origin (endo-, meso-, ectoderm) of the tumor tissue. Based on the findings of thirteen tumor entities, we identified three resistance groups, where Group 1 (endodermal origin) prominently indicates NRF2-pathway activation, Group 2 (mesodermal origin, primordial germ cells) shares elevated DNA repair mechanisms and decreased apoptosis induction, and Group 3 (ectodermal and paraxial mesodermal origin) commonly presents deregulated apoptosis induction and alternating pathways as the main cisplatin-induced resistance mechanisms. This review further proposes potential and novel therapeutic strategies to improve the outcome of cisplatin-based chemotherapy.
KW - Apoptosis/genetics
KW - Cisplatin/pharmacology
KW - DNA Repair/genetics
KW - Disease Progression
KW - Drug Resistance, Neoplasm/genetics
KW - Humans
KW - Neoplasms/drug therapy
U2 - 10.1016/j.canlet.2021.07.037
DO - 10.1016/j.canlet.2021.07.037
M3 - SCORING: Review article
C2 - 34320371
VL - 519
SP - 199
EP - 210
JO - CANCER LETT
JF - CANCER LETT
SN - 0304-3835
ER -
